I am a new faculty member in Neurology with fellowship training in Cognitive Neurology. I have put forth great effort to do research during my clinical training, but am seeking funding to release me from my current heavy burden of clinical responsibilities in order to develop as an independent investigator. My career development plan includes courses in neuroscience, cognitive neuroscience, behavioral pharmacology, statistics, and ethics, and regular guidance meetings with my mentor (Dr. Robert Bornstein, a neuropsychologist experienced in frontal lobe research) and collaborators. My previous research has shown that individuals with high-functioning adults with autism spectrum disorder (ASD) have impaired flexibility of the semantic network. This may relate to other problems with context utilization, problem solving, and social functioning in ASD. My previous research has also demonstrated a noradrenergic modulation of cognitive flexibility in normal individuals. I wish to further explore the modulation of cognitive flexibility. My hypothesis is that noradrenergic modulation of cognitive flexibility is specific to the noradrenergic system among catecholamines, that noradrenergic modulation of cognitive flexibility can occur with long-term treatment, and that noradrenergie antagonism can influence cognitive flexibility in ASD. My first Specific Aim is to further study the influence of catecholamines on cognitive flexibility. I will first test modulation of cognitive flexibility with varying doses of noradrenergic agents, and will test whether long-term propranolol can have the same effect as single-dose propranolol. I will then test whether dopaminergic agents can yield the same finding with cognitive flexibility. My second Aim is to study the effects of stress and propranolol on cognitive flexibility. I will test whether propranolol can reverse the impairment in cognitive flexibility that results from situational stressors. My third Aim is to learn the effects of noradrenergic antagonism on cognitive flexibility in individuals with ASD. I will test whether propranolol has a greater effect on cognitive flexibility in individuals with ASD than in matched controls. With better understanding of modulation of cognitive flexibility, future studies can further test noradrenergic modulation of cognitive flexibility in ASD. My long-term goal is to study neuropharmacology and cognitive neuroscience and look for benefits in cognitively impaired patients, with a particular focus on high-functioning adults with ASD. OSU and my outside consultants are well equipped for my current and future research goals, with ongoing autism research, possible potential for future high-field fMRI, and strong neuroscience training. [unreadable] [unreadable]